Combination of atorvastatin and gemfibrozil plus physical activity: an animal model of statin/fibrate-induced myopathy.

INTRODUCTION: Drug-induced myopathy is among the most common causes of muscle disease. Lipid-lowering drugs, primarily the statins as inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, are a common cause of myopathy. Statin-fibrate combination potentially increases risk for myopathy and rhabdomyolysis. Blood levels of the enzymes creatine kinase (CK), aldolase and lactate dehydrogenase (LDH) increase during myopathy. Exercise may be a trigger for statin-associated muscle symptoms (SAMS). METHODS: In this study a model of myopathy induction was designed via combination of oral atorvastatin, gemfibrozil and exercise for ten days in rats. To maximise exercise, the rats were placed in a pool of water and allowed to swim before sinking in the last three days. Finally, the mean of swimming tolerance times and blood levels of creatine kinase, aldolase and lactate dehydrogenase were measured. RESULTS: The results showed a significantly (p < 0.05) decreased swimming tolerance time and elevated enzyme levels in rats receiving atorvastatin (ATV) and gemfibrozil (GMF) plus exercise compared with those rats in other groups. This animal model can be used to evaluate the effects of medication on reduction of statin/fibrate-induced myopathy.

Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis: A systematic review and indirect comparison.

OBJECTIVES: There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. METHODS: This meta-analysis was performed according to the PRISMA statement protocol. A systematic literature search of three major bibliographic databases (Scopus, PubMed, and Cochran) was performed until June 30, 2018. This review included studies that evaluated the efficacy of etrolizumab or infliximab in ulcerative colitis and were placebo controlled randomized trials. Pooled data from each treatment were indirectly compared using Bucher's method. RESULTS: Seven trials were sufficiently homogeneous to be used for indirect comparison of the induction phase of the treatment. There were no significant differences in clinical remission and serious adverse events between etrolizumab and infliximab. Moreover, adverse events of etrolizumab were significantly less than those of infliximab. However, further trials are required to compare other parameters of efficacy such as the clinical response and mucosal healing of etrolizumab with infliximab in anti-TNF alpha naïve patients.

Impact of licorice root on the burn healing process: A double-blinded randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the known side effects of many synthetic drugs, the use of herbal and natural substances in treating diseases such as burns has been considered. licorice is a herbal medicine whose stem and underground roots are used in traditional medicine in many countries, including Iran, for anti-inflammatory, stomach ulcer healing, and antimicrobial purposes. AIM OF THE STUDY: This study investigated the healing effect of hydroalcoholic extract of licorice root on the wound healing process caused by second-degree burns. METHODS: The hydroalcoholic extract of licorice was prepared in ethanol solvent, and then the licorice hydrogel product was designed using gelling compounds. Then, in a double-blinded randomized clinical trial, 50 patients with second-degree burns were selected based on inclusion criteria from the patients referred to Yazd Hospital and Isfahan Hospital. Participants were randomly divided into two groups: the control group receiving hydrogel without extract and the intervention group receiving hydrogel containing licorice root hydroalcoholic extract. The intervention lasted for 15 days, and during this period, the wound-healing process was evaluated on days 1, 3, 6, 10, and 15. Data were analyzed using SPSS software with independent T-test and Mann-Whitney U tests with a maximum error of 5 %. RESULTS: The rate of inflammation (From the 3rd day to the 10th day), redness (From the 6th day to the 15th day), pain (on the 3rd day), and burning (From the 3rd day to the 15th day) of the wound in the group that used the hydrogel-containing hydroalcoholic extract of licorice root was significantly lower than in the control group (P < 0.05), and the healing process was significantly faster than the control group. CONCLUSION: Hydroalcoholic extract of licorice root can accelerate the healing process of second-degree burns.

Ascorbic Acid Significantly Decreases Creatine Kinase Plasma Levels in an Animal Model of Statin/Fibrate-Induced Myopathy.

BACKGROUND: Myopathy is one of the side effects of lipid-lowering drugs, especially statins and particularly when combined with a fibrate. To diagnose myopathy and determine its severity, the plasma levels of three enzymes, creatine kinase (CK), aldolase, and lactate dehydrogenase (LDH), are routinely measured. Physical exercise can aggravate the statin-associated muscular disease. The question is whether antioxidants like ascorbic acid (Vit. C) can prevent such myopathy. METHODS: In this experiment, a combination of atorvastatin (ATV, 80 mg/kg/day) and gemfibrozil (GMF, 1000 mg/kg/day) orally for 10 days as well as exercise as forced swimming on days 8, 9, and 10 were used to induce myopathy. Ascorbic acid (50 mg/kg/day, orally) was added to ATV/GMF plus exercise regimen throughout the 10 days in the treatment group. Mean blood levels of CK, aldolase, and LDH were measured in addition to swimming tolerance times. RESULTS: There was a significantly higher swimming tolerance time (P < 0.05) and lower CK levels (P < 0.01) in rats receiving ATV/GMF/Vit. C plus exercise compared with rats not taking Vit. C. LDH and aldolase did not decrease significantly. CONCLUSION: The results of this study showed that Vit. C can be effective in preventing myopathy caused by fat-lowering drugs.

Evaluation of the central and peripheral effects of doxepin on carrageenan-induced inflammatory paw edema in rat.

The anti-inflammatory effects of anti-depressants have been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), has some special properties in comparison with the other members of its family. It has some H1, H2, alpha-1 adrenergic and muscarinic receptor blocking effects. It revealed also anti-nociceptive and relatively potent sedative effects. This study was aimed to evaluate its possible anti-inflammatory effect in a well-established animal model. Male Wistar rats weighing 200-250 g were used in carrageenan-induced inflammatory paw edema model. The test and control drugs were injected by intraperitoneal (i.p.) and intracerebral (i.c.v.) routes. The anti-inflammatory activity of doxepin (15, 30 and 60 mg/kg, i.p. and 50 and 100 µg/rat, i.c.v.) and the reference drug, dexamethasone (2 mg/kg, i.p.) were evaluated by determination and comparison of some involved biological markers including the paw volume, cytokine levels (interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNFα)), myeloperoxidase (MPO) activity and histopathological parameters. All i.p. doses of doxepin showed significant anti-inflammatory effect. It also significantly reduced MPO activity and cytokine levels and improved histopathologic parameters of carrageenan-injected paw tissues. I.c.v. administration of the drug did not show any significant reduction of carrageenan-induced paw edema. Although the exact mechanism of the anti-inflammatory effect of doxepin is not clear, it seems that reduced leukocyte migration and pro-inflammatory cytokines play important role in its anti-inflammatory effect. Also central sites are not involved in the anti-inflammatory effect of the drug.

Evaluation of central and peripheral effects of doxepin on acetic acid-induced colitis in rat and the involved mechanisms.

Anti-colitis effect of antidepressants has been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), with potent H1, H2, alpha1 adrenergic and muscarinic receptor blocking effects could be a good candidate for investigation for its anti-colitis activity. Moreover high prevalence of depression in patients who suffer from IBD (inflammatory bowel disease), defends this idea that adjuvant therapy with an antidepressant drug which has anti-inflammatory effect, may exert favorable effects in the control of the disease. In this study colitis was induced by acetic acid instillation into rat's colon. Doxepin was injected by intraperitoneal (10, 20, 40 mg/kg, twice daily, i.p.) or intracerebroventricular (50 and 100 microgram/rat, i.c.v.) routes to separate the mechanisms are absolutely exerted centrally or mediated both centrally and peripherally prior to induction of colitis. Dexamethasone (2 mg/kg/day, i.p.) was used as reference drug. All the treatments continued for three successive days. The effectiveness of drug was evaluated by determination of cytokines (TNFα, IL6 and IL1ß) and myeloperoxidase (MPO) activity as well as macroscopic scores and histopathological parameters. Doxepin after i.p. administration was effective to reduce colitis severity through reduction in the macroscopic and microscopic colonic parameters, MPO activity and cytokines levels. Intracerebroventricular administration of the drug in contrast, did not show any significant protective effect suggesting no important central mechanisms for anti-colitis activity of doxepin. Doxepin as an ancient antidepressive drug has anti-colitis and anti-inflammatory properties which are mainly exerted peripherally so it could be introduced as a good candidate for depressed people who suffered from IBD disorders.

Global rainfall erosivity assessment based on high-temporal resolution rainfall records.

The exposure of the Earth's surface to the energetic input of rainfall is one of the key factors controlling water erosion. While water erosion is identified as the most serious cause of soil degradation globally, global patterns of rainfall erosivity remain poorly quantified and estimates have large uncertainties. This hampers the implementation of effective soil degradation mitigation and restoration strategies. Quantifying rainfall erosivity is challenging as it requires high temporal resolution(<30 min) and high fidelity rainfall recordings. We present the results of an extensive global data collection effort whereby we estimated rainfall erosivity for 3,625 stations covering 63 countries. This first ever Global Rainfall Erosivity Database was used to develop a global erosivity map at 30 arc-seconds(~1 km) based on a Gaussian Process Regression(GPR). Globally, the mean rainfall erosivity was estimated to be 2,190 MJ mm ha-1 h-1 yr-1, with the highest values in South America and the Caribbean countries, Central east Africa and South east Asia. The lowest values are mainly found in Canada, the Russian Federation, Northern Europe, Northern Africa and the Middle East. The tropical climate zone has the highest mean rainfall erosivity followed by the temperate whereas the lowest mean was estimated in the cold climate zone.